A BODIPY-naphtholimine-BF2 dyad for precision photodynamic therapy, targeting and dual imaging of endoplasmic reticulum and lipid droplets in cancer

Abstract

Currently effective therapeutic modalities for pancreatic ductal adenocarcinoma (PDAC) is not available, leading to gloomy prognosis and ~6-months median patient survival. Recent advances showed the promise of photodynamic therapy (PDT) for PDAC patients. Next generation photosensitizers (PS) are based on "organelle-targeted-PDT" and provides new paradigm in the field of precision medicines to address the current challenge for treating PDAC. In this investigation, we have constructed a novel PS, named as NbB, for precise targeting of endoplasmic reticulum (ER) and lipid droplets (LD) in PDAC, as malignant PDAC cells are heavily relying on ER for hormone synthesis. Our live cell imaging and fluorescence recovery after photobleaching (FRAP) experiments revealed that NbB is instantly targeted to ER and LD and show simultaneous dual fluorescence colour due to polar and non-polar milieu of ER and LD. Interestingly, the same molecule generates triplet state and singlet oxygen efficiently and cause robust ER stress and apoptosis in two different PDAC cells in the presence of light. Together, we present, for the first time, a potential next generation precision medicine for ER-LD organelle specific imaging and PDT of pancreatic cancer.